This project represents a comprehensive multidiscipline study of erythema multiforme, a common disorder with significant complications. The primary purpose of this study is to characterize the pathogenesis of erythema multiforme, which we hypothesize involves immunologically-mediated tissue damage initiated by a variety of foreign antigens. Cases of erythema multiforme will be studied for evidence of circulating immune complexes and for evidence of cytotoxicity to epidermal cells. Measurement of activity of the complement system, assays for immune complexes (I125C1q binding and Raji cell), and quantitation of cryoimmunoglobulins will be performed. In order to identify foreign antigens important in the pathogenesis, the components of the cryoprecipitates, both antibodies and antigens, will be specifically characterized. The presence of antibodies which mediate antibody dependent cellular cytotoxicity to epidermal cells will be evaluated. The presence of immunoreactants in skin lesions will be determined by immunofluorescence and electron microscopy. In all cases studied, careful clinical data from history and physical examination, histological data from light microscopic and electron microscopic examinations of skin lesions, and etiological data from history and laboratory evaluation will be collected. By correlating data from the clinical, histological, etiological, and pathogenetic aspects of the study, we will be able to better understand the syndrome. Furthermore, we may be able to identify antigens and antibodies that initiate the process. A much needed double-blind therapeutic study glucocorticoid therapy of erythema multiforme will be performed.